title: IRF-1-binding site in the first intron mediates interferon-γ-induced optineurin promoter activation.
abstract: Optineurin is an adaptor protein involved in signal transduction, membrane vesicle trafficking and autophagy. Optineurin expression is induced by cytokines. Previously we have shown that tumor necrosis factor-α activates optineurin promoter through NF-κB-binding site in the core promoter. However, this promoter was not activated by interferon-γ. Here, we report identification of a functional IRF-1-binding site in the first intron of human optineurin gene that mediates interferon-γ-induced activation of the promoter. Optineurin promoter, containing the contiguous intronic sequences with IRF-1 responsive sites, is strongly activated by IRF-1. Mutational inactivation of IRF-1 site resulted in loss of activation of the promoter by interferon-γ and also by IRF-1. We also show that IRF-1 cooperates with NF-κB to activate optineurin promoter. The synergistic effect of these two transcription factors (IRF-1 and NF-κB) may be involved in cooperative induction of optineurin promoter by interferon-γ and tumor necrosis factor-α.
authors.affiliation: Centre for Cellular and Molecular Biology, Council of Scientific and Industrial Research, Uppal Road, Hyderabad 500 007, India. cheru@ccmb.res.in
authors.forename: Cherukuri
authors.initials: C
authors.lastname: Sudhakar
authors.forename: Vipul
authors.initials: V
authors.lastname: Vaibhava
authors.forename: Ghanshyam
authors.initials: G
authors.lastname: Swarup
mesh_terms: D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D007438:Introns / Q000235:genetics*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding / Q000187:drug effects / Q000235:genetics; D035582:Transcription Factor TFIIIA / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D018797:Cell Cycle Proteins; C494257:IRF1 protein, human; D050856:Interferon Regulatory Factor-1; D026901:Membrane Transport Proteins; D016328:NF-kappa B; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: ChIP; IFN; IFN-γ; IRF-1; LC3; Optineurin; Promoter activation; STAT; TNF-α; chromatin immunoprecipitation; interferon; interferon regulatory factor 1; microtubule associated light chain 3; signal transducer and activator of transcription; tumor necrosis factor-α